Azetidines ring synthesis

Azete, trisdimethylamino-isolation, 7, 278 Azetes, 7, 237-284, 278-284 benzo fused, 7, 278 benzodiazepine fused applications, 7, 284 fused ring, 7, 341-362 structure, 7, 360 2,3-naphtho fusion, 7, 278 reactivity, 7, 279 structure, 7, 278 synthesis, 7, 282-283 Azetidine, acylring expansion, 7, 241 synthesis, 7, 246 Azetidine, 3-acyl-irradiation, 7, 239 synthesis, 7, 246 Azetidine, N-acyl-synthesis, 7, 245 Azetidine, alkyl-synthesis, 7, 246 Azetidine, 3-alkylthio-synthesis, 7, 246 Azetidine, 3-amino-synthesis, 7, 246 Azetidine, N-amino-oxidation, 7, 241 synthesis, 7, 246 Azetidine, aryl-synthesis, 7, 246... 

A structurally unrelated agent is tazadolene (40). The synthesis of tazadolene begins with P-keto ester 37 and subsequent enamine formation with 3-amino-1-propanol followed by hydrogenolysis to give 38. This phenylhydroxymethyl compound is then dehydrated with hydrochloride acid to form olefin 39. Treatment with bromine and triphenylphosphine effects cycliza-tion to form the azetidine ring of tazadolene [10]. 

The four-membered azetidine ring remains unaffected by sodium in liquid ammonia, 94 methanolic ammonia, 95 5M barium hydroxide at 100 °C for 24 hours, 87 sodium hydroxide under ester saponification conditions, 87 HC1 at room temperature, 96,97 catalytic hydrogenation under normal conditions, 87,95 and ozonolysisJ87 Correspondingly, as observed for proline, the azetidine-2-carboxylic acid (2) raises no particular difficulties in the synthesis of related peptides. 

In 1050 Sheehan and Bose reported the formation of an asetidi-none by intramolecular alkylation of an -haloa( ]aminomalonk ester (Eq. 40). ThiB was the first example of a -lactam synthesis in which the amide bond was first established, and it is the only case 3 which any azetidine ring has been formed by cydisation of a hetero-ehain at a C—C bond. 

Azetidines, whose structures have been found in many natural products, constitute an important class of compounds, because of their interesting pharmacological activities and synthetic utility. Whereas the strain associated with the azetidine ring system leads to difficulties in its synthesis, functionalization... 

Nocquet, P.-A., Hazelard, D., Compain, P. (2011). Synthesis of spirocyclo-propyl yl ctams by a highly stereoselective tandem intramolecular azetidine ring-opening/closing cascade reaction. European Journal of Organic Chemistry, 2011,6619-6623. 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

Azetidine, 7V-bromo-, 7, 240 Azetidine, AT-r-butyl- N NMR, 7, 11 Azetidine, AT-t-butyl-3-chloro-transannular nucleophilic attack, 7, 25 Azetidine, 3-chloro-isomerization, 7, 42 Azetidine, AT-chloro-, 7, 240 dehydrohalogenation, 7, 275 Azetidine, 7V-chloro-2-methyl-inversion, 7, 7 Azetidine, 3-halo-synthesis, 7, 246 Azetidine, AT-halo-synthesis, 7, 246 Azetidine, AT-hydroxy-synthesis, 7, 271 Azetidine, 2-imino-stability, 7, 256 Azetidine, 2-methoxy-synthesis, 7, 246 Azetidine, 2-methyl-circular dichroism, 7, 239 optical rotatory dispersion, 7, 239 Azetidine, AT-nitroso-deoxygenation, 7, 241 oxidation, 7, 240 synthesis, 7, 246 Azetidine, thioacyl-ring expansion, 7, 241 Azetidine-4-carboxylic acid, 2-oxo-oxidative decarboxylation, 7, 251 Azetidine-2-carboxylic acids absolute configuration, 7, 239 azetidin-2-ones from, 7, 263 synthesis, 7, 246... 

Azetidin-2-one, l-benzyl-3,3,4-triphenyl-, 7, 249 Azetidin-2-one, l-(2-bromophenyl)-X-ray crystallography, 7, 247 Azetidin-2-one, 3-carboxy-synthesis, 7, 262 Azetidin-2-one, 3-halo-synthesis, 7, 77 ring contraction, 7, 81-82 Azetidin-2-one, 4-imino-IR spectroscopy, 7, 248 Azetidin-2-one, 1-phenyl-irradiation, 7, 255 Azetidin-2-one, 4-phenyl-reductive ring cleavage, 7, 252 Azetidin-2-one, 4-thio-IR spectroscopy, 7, 248 Azetidinones bicyclic, 7, 348-356 C NMR, 7, 348 H NMR, 7, 348 reactivity, 7, 356-358 spectroscopy, 7, 357 structure, 7, 349 synthesis, 7, 358-359 fused ring... 

Joyeau, R. Felk, A. Guillaume, S. Vergely, I. Doucet, C. Boggetto, N. Reboud-Ravaux, M. Synthesis and inhibition of human leucocyte elastase by functionalized V-aryl azetidin-2-ones effect of different substituents on the aromatic ring. J. Pharm. Pharmacol. 1996, 48, 1218-1230. 

P-Lactams have been used as a synthon for the preparation of a vast array of compounds. It has been reported that the reduction of 4-(haloalkyl)azetidin-2-ones with LiAlhL is a powerful method for the synthesis of stereodefined aziridines and azetidines <06OL1101>. However, reduction of 4-(haloalkyl)azetidin-2-ones with chloroalane afforded 2-(haloalkyl)azetidines, which were rearranged to 3,4-cw-disubstituted pyrrolidines and piperidines 32 <060L1105>. During these rearrangements, bicyclic azetidinium intermediates were formed which were ring opened by halides. The synthesis of a peptide-... 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

Examples of the synthesis of fused-ring azetidines by ring closure onto a preformed azetidine are uncommon, in contrast to approaches used for the preparation of fused ring azetidinones (see Sections 5.12.3, 5.11.4.4 and 5.10.4.3). The l,3-diazabicyclo[3.2.0]hep-tane derivative (48) was prepared (72JOC516) by cyclization with DCC of the carbamoyl-azetidine followed by thermal rearrangement of the intermediate thiazolidinone (Scheme 6). 

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